Bacterial infection of CNS

Question 1

what are the 4 major symptoms of meningitis?

Answer 1

1. headache
2. stiff neck
3. fever
4. photophobia

Question 2

Neisseria meningitidis bacteriology

Answer 2

1. gram negative diplococci
2. facultative intracellular
3. human-restricted
4. encapsulated (nonencapsulated strains are nonpathogenic)

Question 3

what is unique about Neisseria meningitidis?

Answer 3

ferments glucose and maltose (not sucrose or lactose)

Question 4

growth of N. meningitidis is inhibited by

Answer 4

trace metals and fatty acids: chocolate agar not blood agar

Question 5

how is N. meningitidis transmitted?

Answer 5

by airborne droplets

Question 6

N. meningitidis colonize

Answer 6

nasopharynx (only resorvoir) –> asymptomatic carrier, common in prisons, dorms, military, family of index case

Question 7

N. meningitidis spread and colonization may be enhanced by

Answer 7

concomitant upper respiratory viral infections

Question 8

Major agents of infectious meningitis

Answer 8

a. Pneumococcus (this lecture)
b. Group B Strep (this lecture)
c. Meningococcus (this lecture)
d. H. influenzae (Unit 6)
e. Syphilis (Unit 1)
f. Lyme (Unit 2)
g. TB (Unit 4)
h. Listeria (Unit 6)
i. Fungi (Unit 4)
j. Enterobacteriaceae (Unit 6)
k. Pseudomonas (Unit 4)
l. Viruses (next lecture)

Question 9

Neisseria meningitidis (meningococcus)
a. Bacteriology

Answer 9

i. Gram(-) diplococci
ii. Human-restricted
iii. Encapsulated
iv. ~13 serotypes
v. Oxidase(+), catalyase(+)
vi. Ferments glucose&maltose, NOT sucrose, lactose
vii. Won’t grow on blood agar; use chocolate agar or Thayer-Martin as
appropriate

Question 10

Pathogenesis of Neisseria meningitidis

i. Transmitted by

Answer 10

airborne droplets

Question 11

ii. Neisseria meningitidis Use

Answer 11

IgA protease to colonize nasopharnyx (only reservoir)

iii. Infection usually resolves without symptoms
1. Controlled by IgG-enhanced complement, neutrophils
2. Lifelong immunity to controlled strain

Question 12

N. meningitidis

Answer 12

iv. Deficiency in Complement C6-C9 predisposes to spread beyond
respiratory sys. Polysaccharide capsule (primary virulence factor) resists
phagocytosis, endotoxin LOS may cause septic shock
v. Bacteria colonize:
1. Joints: septic arthritis
2. Meninges: meningitis, fatal if untreated, may still cause brain damage with treatment
vi. Can cause epidemics of meningitis

Question 13

N. meningitidis Diagnosis

i. Exam:
1. Septic arthritis:

Answer 13

joint pain, draw joint fluid
2. Meningitis
a. Adults: classic fever/headache/stiff neck
b. Peds (2/3 of cases): irritability, convulsions, lassitude,
fever, abdominal discomfort/vomiting
c. Both: draw CSF, admit

Question 14

N. meningitidis Meningococcemia?

Answer 14

a. Fever and hourly-spreading rash
b. Draw blood and CSF, admit to ICU
c. Waterhouse-Friderichen syndrome: high fever, shock,
widespread purpura, DIC, thrombocytopenia, destruction of adrenal glands, 50% fatal

Question 15

N. meningitidis Lab

Answer 15

1. Septic arthritis: Gram stain, culture on chocolate agar
2. Meningitis: Gram stain, culture on chocolate agar, CSF smear for Gram(-) cocci
3. Meningococcemia: Gram stain, culture on chocolate agar, blood tests for DIC
4. PCR tests available

Question 16

N. meningitidis treatment

Answer 16

Treatment

i. Penicillin G, alternates ceftriaxone, cefotaxime, cefuroxime, chloramphenicol
ii. Meningococcemia: also admit to ICU, support circulation and renal function
iii. NO STEROIDS
iv. Prevention
1. Vaccine
2. Antibiotic prophylaxis for close contacts

Question 17

GBS

a. Organism
i. GBS = Group B Strep =

Answer 17

= S. agalactiae
ii. Gram(+) cocci
iii. Beta-hemolytic
iv. Encapsulated
v. Polysaccharide toxin virulence factor
vi. Serotype-specific antibody-mediated immunity
vii. Normal vaginal flora (15-45%),
viii. May also be normal flora in GI and upper respiratory tract
ix. Very seldom causes disease in previously-healthy adults; may cause
bacteremia, cellulitis, UTI with predisposing factors

Question 18

GBS Pathogenesis

i. 1-2% of neonates of GBS+ mothers develop invasive disease most common cause of

Answer 18

neonatal sepsis,

Question 19

2 types of neonatal sepsis by GBS?

Answer 19

1. Early disease
   a. Pneumonia w/ bacteremia
   b. Presents 1-7d postpartum
   c. Appears to be more common in US than developing world; may be masked by other causes of neonatal death
2. Late disease
   a. Bacteremia w/ meningitis
   b. Presents 1-12wk postpartum
   c. Usually Serotype 3
3. Prematurity and prolonged rupture of membranes are risk factors for both

Question 20

GBS disease also may be seen in geriatric patients with pre-existing major health conditions

Answer 20

1. Diabetes
2. Malignancy
3. Congestive heart failure
4. These rare infections seem to be becoming more common; probably both improved reporting and also population becoming older, more immunosuppressed

Question 21

Two groups at risk of GBS disease

Answer 21

1. Pregnant/neonate: more common
   a. Mother develops uterine infection or UTI
   b. Neonate develops pneumonia (early) or meningitis (late)
2. Elderly with comorbidity: less common, more lethal

Question 22

Diagnosis for GBS

Answer 22

i. Gram stain and culture of appropriate sample (tissue biopsy, aspirate, CSF)
ii. CT/MRI for abscesses
iii. Echocardiogram for endocarditis
iv. Some antigen tests are also available for blood, urine, CSF

Question 23

treatment for GBS?

Answer 23

1. penicillin or amoxicillin
2. if allergic vancomycin
3. surgical intervention may be needed, primarily in the geriatirc with predispostion cases

Question 24

Prevention of GBS

Answer 24

i. Test term-pregnant patients for GBS by swab and culture. If positive:
ii. Intrapartum (during delivery) IV administration of penicillin or amoxicillin
iii. If allergic, use clindamycin or erythromycin, but resistant strains exist
iv. Strategy has reduced early disease in US over past decade, but there are questions about the sensitivity of the culture and PCR tests.

Question 25

Pneumococcus | a. Organism

Answer 25

i. Staph pneumoniae ii. Gram(+), catalase(-), facultative anaerobe iii. In culture, form diplococci in chains iv. Pathogenic strains are encapsulated v. The most common cause of community-acquired pneumonia, bacterial meningitis, bacteremia, and otitis media, as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis vi. A major childhood pathogen worldwide with deaths from pneumonia and meningitis

Question 26

Meningococci encode 3 major virulence factors:

Answer 26

Meningococci encode 3 major virulence factors: 1. IgA Protease: cleaves IgA, reduces defense of mucus membrane 2. Polysaccharide capsule (resists phagocytosis) 3. Endotoxin LOS (component of Gram(-) cell wall, causes fever, shock)

Question 27

If enters bloodstream: meningococcemia Colonizes favorite sites Joints: septic arthritis Meninges: meningitis, fatal if untreated, still may kill (

Answer 27

in 2-18yr age range

Question 28

Pathogenesis of meningococcemia, cont:

Answer 28

Ab to capsule is protective  vaccine | Deficiency in late-acting complement components C6-C9 is predisposing for complications

Question 29

N. meningitidis Diagnosis: Exam

Answer 29

1/3 cases adult, 2/3 pediatric Septic arthritis: joint pain - draw joint fluid Meningitis: Adults: classic fever, headache, stiff neck, progression to coma is bad Young children: irritability, convulsions, lassitude, fever, abdominal discomfort/vomiting Both: draw CSF, admit

Question 30

Meningococcemia:

Answer 30

1. Fever and hourly-spreading petechial skin rash (may be hard to see on dark skin) - draw blood and CSF, admit to ICU. 2. Rarely, may be present for weeks before symptoms become alarming (“chronic”). 3. 5-15% develop 50%-fatal Waterhouse-Friderichen syndrome: high fever, shock, widespread purpura, disseminated intravascular coagulation (DIC), thrombocytopenia, destruction of adrenal glands.

Question 31

Waterhouse-Friderichen syndrome:

Answer 31

high fever, shock, widespread purpura, disseminated intravascular coagulation (DIC), thrombocytopenia, destruction of adrenal glands.

Question 32

Septic arthritis:

Answer 32

Joint fluid: Gram stain and culture on chocolate agar

Question 33

Meningitis: CSF:

Answer 33

increased PMNs, Gram stain (~50% sensitive) and culture on chocolate agar, Gram(-) cocci in CSF smear suffice for diagnosis, alternatively, latex agglutination test for capsule polysaccharide in CSF

Question 34

Meningococcemia:

Answer 34

Blood: Gram stain and culture on chocolate agar, set of tests for DIC

Question 35

N. Meningitidis Treatment

Answer 35

Penicillin G unless allergic, or local history of drug resistance Alternates: Ceftriaxone, cefotaxime, and cefuroxime; if severely allergic to penicillin, chloramphenicol Fulminant meningococcemia: admit to ICU, support circulation and renal function Prescribing glucocorticosteriods for the rash and arthritis would be very bad, even though they are recommended for some other types of meningitis

Question 36

prevention of N. Meningitidis

Answer 36

Close contacts of index case get prophylactic rifampin, ceftriaxone, or ciprofloxacin (excreted efficiently into saliva)

Question 37

GBS = Group B Strep =

Answer 37

S. agalactiae Encapsulated Gram(+) cocci Beta-hemolytic Polysaccharide toxin virulence factor Pilus-like attachment virulence factor Serotype-specific antibody-mediated immunity Normal vaginal flora (15-45%), transmits to neonate shortly before and during delivery May also be normal flora in GI and upper respiratory tract

Question 38

GBS Risk Group 1 of 2: Neonate

Answer 38

1-2% of neonates of GBS+ mothers develop invasive disease Most common cause of neonatal sepsis Usually Serotype 3 (of 10) ``` 2 types: Early disease Pneumonia w/ bacteremia Presents 1-7d postpartum Prevented by intrapartum IV antibiotics Late disease Bacteremia w/ meningitis Presents 1-12wk postpartum ```

Question 39

GBS lab

Answer 39

CAMP test: CAMP factor secreted by B-group strep (and Listeria) enhances activity of β-hemolysin from S. aureus

Question 40

GBS lab

Answer 40

Hippurase/Hippurate Test: Colorimetric test for hippurase, produced by GBS, Gardnerella vaginalis, Campylobacter jejuni, Listeria monocytogenes

Question 41

GBS treatment

Answer 41

1. IV Penicillin or amoxicillin 2. If allergic, vancomycin 3. Surgical intervention may be needed: heart valve replacement for endocarditis, abscess removal for cellulitis, amputation for diabetic foot

Question 42

``` Strep pneumoniae Gram(+), catalase(-), facultative anaerobe In culture, form diplococci in chains Pathogenic strains are encapsulated The most common cause of ```

Answer 42

community-acquired pneumonia, bacterial meningitis, bacteremia, and otitis media, as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis

Question 43

Pneumococcus exam

Answer 43

Diseases of direct extension (Non-Invasive Disease): sinusitis, otitis media, bronchitis, pneumonia Pneumonia causes significant morbidity and mortality (10-20%) Patient looks ill, anxious Predispositions: asthma, COPD, chronic bronchitis, smoking or frequent exposure to cigarette smoke Stethoscope: can hear rales in most patients, dullness to percussion in half (Heart and Lung Sounds Audio Workshop: bronchial breath and late-inspiratory crackles) Radiology findings Adolescents and adults: lobar consolidation Infants and young children: scattered parenchemyal consolidation, bronchopneumonia

Question 44

Staph pneumonia

Answer 44

Non-invasive Disease can usually be treated based on exam, optional Gram stain Invasive Disease: Gram stain and culture of appropriate samples (blood, sputum, CSF, abscess aspirates or biopsies). Blood cultures usually positive. Begin antibiotic-sensitivity testing Urine-antigen testing is available, useful for pneumonia in young children who don’t produce enough sputum for testing. Meningitis spinal tap findings are typical of bacterial meningitis: Elevated opening pressure Elevated WBC count and neutrophil level Elevated protein Decreased glucose Highly elevated lactic acid Gram stain and culture are positive unless antibiotic treatment began >4hrs prior to tap

Question 45

Pneumococcus Prevention

Answer 45

Prevnar7 vaccine raises protective IgG against the capsules of the seven serotypes that most commonly caused invasive disease prior to 2000. Universal childhood vaccination with Prevnar7 starting in 2000 knocked down levels of invasive disease 90% Childhood cases of invasive disease caused by those serotypes essentially disappeared (more effective than anyone expected) Rates of carriage of those serotypes dropped as herd immunity was achieved Rates of disease caused by other serotypes of pneumococcus increased (“replacement disease”)

Question 46

Pneumococcus prevention

Answer 46

Prevnar13 vaccine, providing coverage for the original seven plus 6 of the newly-problematic serotypes, is now available. May be used for childhood vaccination series May be given as a booster to those who received the Prevnar7 series